Diabetes and Glucose Control
How High Blood Sugar Damages Tissues And Promotes Aging
Glucose toxicity is mediated primarily by three tissue-damaging processes: glycation, inflammation, and free radical damage. These interrelated processes contribute to complications of diabetes including endothelial dysfunction, atherosclerosis, diabetic nephropathy, and other chronic diseases (Yamagishi 2011; Yan 2014; de Carvalho Vidigal 2012; Wada 2013; de Vries 2014; Lontchi-Yimagou 2013).
Glycation and AGEs
Glycation is a process whereby sugars such as glucose bond to proteins, fats, and nucleic acids in an uncontrolled fashion. This results in the formation of toxic compounds called advanced glycation end products, or AGEs. The accumulation of AGEs in the body irreversibly modifies the structure and function of proteins such as collagen and elastin. These damaged proteins can become joined together through a mechanism called crosslinking, which causes increased stiffness and loss of elasticity in several tissues throughout the body (Nawale 2006; Simm 2013). Glycation and AGEs contribute to the aging process and age-related diseases as well as diabetic complications (Semba 2010; van Heijst 2005; Simm 2013; Nawale 2006).
One study showed plasma levels of AGEs were significantly higher in type 2 diabetic patients compared with nondiabetics. In addition, patients with diabetic complications had significantly higher levels of AGEs compared with complication-free patients. This study also showed a strong correlation between high levels of AGEs and elevated glycated hemoglobin, or hemoglobin A1C—a blood test that reflects average blood sugar levels over a 60- to 90-day period by measuring the amount of hemoglobin that has undergone glycation (Jakus 2014; Bozkaya 2010; ADA 2014a). A study in patients with type 2 diabetes followed over 10 years found that higher levels of blood AGEs predicted cardiovascular events (Hanssen 2015).
This same glycation process that “ages” our body is responsible for the browning reaction that occurs when foods are cooked at high temperatures. When meat is seared or potatoes are fried, AGEs are created (Uribarri 2010). These dietary AGEs can be absorbed into the circulation and remain in the body long enough to cause tissue damage (Vlassara 2014; Luevano-Contreras 2013). Food preparation methods that utilize high heat, such as frying, grilling, and broiling, lead to the formation of more AGEs, while cooking at lower temperatures, shorter cooking times, steaming, boiling, and the use of acids like lemon juice or vinegar in cooking minimize AGE formation (Uribarri 2010). A detailed examination of dietary AGEs and ways to avoid them is available in the Life Extension Magazine article “Are You Cooking Yourself to Death?”.
The antidiabetic drug metformin, amino acid derivative carnosine, and B-vitamin derivatives benfotiamine and pyridoxal-5’-phosphate are examples of agents that mitigate glycation- and AGE-related tissue damage (Ceriello 2009; Schurman 2008; Miyazawa 2012; Nagai 2014; Hipkiss 2005).
Acute inflammation is necessary to fight infections and repair damaged tissue. However, long-term, unabated inflammation can lead to chronic disease. Chronic, low-grade inflammation is a major feature of diabetes and its complications, particularly cardiovascular disease. Persistent high blood sugar, excess abdominal fat, and insulin resistance cause chronic inflammation. Acute, excessive postprandial blood sugar surges can also induce inflammation; foods high in AGEs can aggravate postprandial inflammation (Dandona 2004; Ota 2014; Agrawal 2014; Lontchi-Yimagou 2013; Nowlin 2012; Calder 2011).
Concentrations of proinflammatory cytokines including TNF-α, C-reactive protein (CRP), and interleukin-6 (IL-6) are increased in diabetes (Nguyen 2012; Lontchi-Yimagou 2013). These cytokines impair beta cell function, lowering insulin secretion (Lontchi-Yimagou 2013; Agrawal 2014).
Proinflammatory cytokines induce negative effects throughout the body. Increased levels of these cytokines “switch on” pathways that cause muscle and bone breakdown and neuronal degeneration, accelerate atherosclerosis, and damage DNA, increasing the risk of death (Kabagambe 2011; Michaud 2013; Kiraly 2015; Xu 2015).
Numerous strategies for combatting inflammation are described in the Chronic Inflammation protocol.
Free Radical Damage
Free radicals are highly reactive, unstable molecules produced in the body as byproducts of normal metabolic processes. They can also be created by environmental factors such as X-rays, ozone, tobacco smoke, and air pollution. If excessive free radicals chronically overwhelm the body’s ability to neutralize them, free radical damage can occur within cells, triggering destructive changes that can lead to degenerative disease and aging (Guo 1999; Venkataraman 2013; Lobo 2010; Ortuno-Sahagun 2014; Masters 1995; Gilgun-Sherki 2004).
Several harmful processes induced by hyperglycemia, including AGE formation, are associated with overproduction of a free radical called superoxide. While reactive oxygen species such as superoxide are a normal byproduct of energy production in mitochondria, superoxide radicals generated by glucose overload may cause diabetic complications (Giacco 2010; Ceriello 2011; Rahman 2007; Sasaki 2012).